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- Kenneth Branagh as Franklin D. Roosevelt
- Cynthia Nixon as Eleanor Roosevelt
- Kathy Bates as Helena Mahoney
- Tim Blake Nelson as Tom Loyless
- Jane Alexander as Sara Delano Roosevelt
- David Paymer as Louis McHenry Howe
- Melissa Ponzio as Lucy Mercer
- Marianne Fraulo as Missy LeHand
- Brian F. Durkin as Elliott Roosevelt
- Turner Dixon as James Roosevelt
- Tripp Hennington as Franklin D. Roosevelt, Jr.
- Sam Frihart as John Roosevelt
- Carrie Adams as Anna Roosevelt
- Wilbur Fitzgerald as Al Smith
- Felicia Day as Eloise Hutchinson